Incidental Mutation 'R0054:Snip1'
| ID |
17167 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Snip1
|
| Ensembl Gene |
ENSMUSG00000050213 |
| Gene Name |
Smad nuclear interacting protein 1 |
| Synonyms |
2410133M08Rik |
| MMRRC Submission |
038348-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R0054 (G1)
|
| Quality Score |
|
|
Status
|
Validated
|
| Chromosome |
4 |
| Chromosomal Location |
124960465-124967835 bp(+) (GRCm39) |
| Type of Mutation |
nonsense |
| DNA Base Change (assembly) |
T to A
at 124966633 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Tyrosine to Stop codon
at position 354
(Y354*)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000060721
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000052183]
|
| AlphaFold |
Q8BIZ6 |
| Predicted Effect |
probably null
Transcript: ENSMUST00000052183
AA Change: Y354*
|
| SMART Domains |
Protein: ENSMUSP00000060721
Gene: ENSMUSG00000050213
AA Change: Y354*
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
6 |
19 |
N/A |
INTRINSIC |
|
low complexity region
|
42 |
56 |
N/A |
INTRINSIC |
|
low complexity region
|
62 |
89 |
N/A |
INTRINSIC |
|
low complexity region
|
132 |
146 |
N/A |
INTRINSIC |
|
FHA
|
267 |
331 |
1.52e-14 |
SMART |
|
low complexity region
|
370 |
378 |
N/A |
INTRINSIC |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000145733
|
| Meta Mutation Damage Score |
0.9755 |
| Coding Region Coverage |
- 1x: 88.8%
- 3x: 85.6%
- 10x: 76.3%
- 20x: 59.9%
|
| Validation Efficiency |
96% (91/95) |
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a protein that contains a coiled-coil motif and C-terminal forkhead-associated (FHA) domain. The encoded protein functions as a transcriptional coactivator that increases c-Myc activity and inhibits transforming growth factor beta (TGF-beta) and nuclear factor kappa-B (NF-kB) signaling. The encoded protein also regulates the stability of cyclin D1 mRNA, and may play a role in cell proliferation and cancer progression. Mutations in this gene are a cause of psychomotor retardation, epilepsy, and craniofacial dysmorphism (PMRED). [provided by RefSeq, Mar 2012]
|
| Allele List at MGI |
All alleles(4) : Targeted(3) Gene trapped(1)
|
| Other mutations in this stock |
Total: 57 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Abcc9 |
A |
G |
6: 142,547,500 (GRCm39) |
|
probably null |
Het |
| Apoa4 |
A |
G |
9: 46,153,822 (GRCm39) |
D141G |
probably benign |
Het |
| Atg9a |
T |
C |
1: 75,161,143 (GRCm39) |
Y701C |
probably damaging |
Het |
| Baz2b |
C |
T |
2: 59,762,510 (GRCm39) |
R922Q |
probably damaging |
Het |
| Bmal2 |
T |
G |
6: 146,731,216 (GRCm39) |
V507G |
probably benign |
Het |
| Brms1 |
T |
A |
19: 5,096,727 (GRCm39) |
C136* |
probably null |
Het |
| Ccdc180 |
T |
A |
4: 45,890,900 (GRCm39) |
V24E |
probably benign |
Het |
| Clec4f |
C |
T |
6: 83,629,911 (GRCm39) |
V216M |
probably benign |
Het |
| Cpd |
C |
G |
11: 76,681,664 (GRCm39) |
G1160R |
probably damaging |
Het |
| Creb5 |
A |
G |
6: 53,424,642 (GRCm39) |
M128V |
probably benign |
Het |
| Ddb2 |
G |
T |
2: 91,065,165 (GRCm39) |
Q87K |
probably benign |
Het |
| Defb41 |
A |
G |
1: 18,321,471 (GRCm39) |
Y48H |
probably damaging |
Het |
| Dido1 |
T |
C |
2: 180,303,267 (GRCm39) |
N1546D |
probably benign |
Het |
| Dmac1 |
A |
G |
4: 75,196,337 (GRCm39) |
V51A |
possibly damaging |
Het |
| Dnajb11 |
C |
T |
16: 22,681,369 (GRCm39) |
A49V |
probably damaging |
Het |
| Dnajc14 |
G |
A |
10: 128,643,448 (GRCm39) |
D457N |
probably damaging |
Het |
| Eif3a |
C |
A |
19: 60,755,264 (GRCm39) |
D973Y |
unknown |
Het |
| Farsb |
T |
A |
1: 78,439,011 (GRCm39) |
K395* |
probably null |
Het |
| Fem1b |
A |
G |
9: 62,704,082 (GRCm39) |
S393P |
probably damaging |
Het |
| Fsip2 |
A |
C |
2: 82,817,299 (GRCm39) |
N4344T |
possibly damaging |
Het |
| Gphn |
A |
G |
12: 78,684,277 (GRCm39) |
S558G |
probably damaging |
Het |
| Gpr142 |
C |
A |
11: 114,689,755 (GRCm39) |
H2Q |
probably benign |
Het |
| Grhpr |
T |
C |
4: 44,988,915 (GRCm39) |
|
probably benign |
Het |
| Grik3 |
C |
A |
4: 125,517,368 (GRCm39) |
N70K |
probably damaging |
Het |
| Gsap |
T |
A |
5: 21,455,933 (GRCm39) |
|
probably benign |
Het |
| Iars1 |
T |
A |
13: 49,846,611 (GRCm39) |
C237S |
probably damaging |
Het |
| Ighv1-9 |
A |
T |
12: 114,547,602 (GRCm39) |
F7L |
probably benign |
Het |
| Ints8 |
A |
G |
4: 11,204,595 (GRCm39) |
|
probably benign |
Het |
| Kcnj16 |
G |
T |
11: 110,915,549 (GRCm39) |
W70C |
probably damaging |
Het |
| Kpna6 |
T |
C |
4: 129,551,251 (GRCm39) |
M85V |
probably benign |
Het |
| Kri1 |
G |
A |
9: 21,186,661 (GRCm39) |
S447L |
probably damaging |
Het |
| Lrp1b |
A |
G |
2: 40,632,829 (GRCm39) |
V3528A |
probably benign |
Het |
| Lrrc46 |
A |
T |
11: 96,929,605 (GRCm39) |
L77Q |
probably damaging |
Het |
| Mrpl44 |
T |
C |
1: 79,757,212 (GRCm39) |
L219S |
probably damaging |
Het |
| Ms4a14 |
T |
C |
19: 11,281,303 (GRCm39) |
I418M |
probably benign |
Het |
| Myo7a |
T |
C |
7: 97,714,905 (GRCm39) |
D112G |
probably damaging |
Het |
| Ncoa3 |
A |
G |
2: 165,897,098 (GRCm39) |
T630A |
possibly damaging |
Het |
| Nsl1 |
T |
C |
1: 190,814,381 (GRCm39) |
L194P |
probably damaging |
Het |
| Or5ac23 |
T |
C |
16: 59,149,428 (GRCm39) |
Y148C |
possibly damaging |
Het |
| Or8u10 |
T |
C |
2: 85,915,705 (GRCm39) |
K139E |
probably benign |
Het |
| Pde4d |
A |
G |
13: 109,876,955 (GRCm39) |
S159G |
probably benign |
Het |
| Pi4ka |
T |
C |
16: 17,142,978 (GRCm39) |
R845G |
probably null |
Het |
| Pld1 |
A |
G |
3: 28,150,033 (GRCm39) |
|
probably benign |
Het |
| Psd |
T |
A |
19: 46,311,781 (GRCm39) |
I300F |
probably damaging |
Het |
| Ptprz1 |
T |
A |
6: 22,986,195 (GRCm39) |
W332R |
probably damaging |
Het |
| Rnf212 |
T |
A |
5: 108,893,530 (GRCm39) |
M70L |
possibly damaging |
Het |
| Sema4f |
A |
G |
6: 82,896,674 (GRCm39) |
|
probably benign |
Het |
| Sez6 |
C |
A |
11: 77,844,699 (GRCm39) |
T7K |
possibly damaging |
Het |
| Skint2 |
T |
C |
4: 112,502,660 (GRCm39) |
I290T |
probably benign |
Het |
| Slc5a3 |
T |
A |
16: 91,874,522 (GRCm39) |
I193N |
probably damaging |
Het |
| Tmco5 |
A |
G |
2: 116,717,768 (GRCm39) |
Y200C |
probably damaging |
Het |
| Tmem87b |
T |
A |
2: 128,673,361 (GRCm39) |
|
probably benign |
Het |
| Trim60 |
T |
C |
8: 65,453,973 (GRCm39) |
E92G |
probably benign |
Het |
| Ttn |
A |
T |
2: 76,626,804 (GRCm39) |
D13067E |
possibly damaging |
Het |
| Ufl1 |
A |
T |
4: 25,269,087 (GRCm39) |
I168N |
probably damaging |
Het |
| Zfp385c |
G |
A |
11: 100,520,782 (GRCm39) |
P293S |
probably benign |
Het |
| Zfp473 |
T |
A |
7: 44,383,899 (GRCm39) |
S144C |
probably damaging |
Het |
|
| Other mutations in Snip1 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL02223:Snip1
|
APN |
4 |
124,966,545 (GRCm39) |
missense |
possibly damaging |
0.66 |
|
R0054:Snip1
|
UTSW |
4 |
124,966,633 (GRCm39) |
nonsense |
probably null |
|
|
R1163:Snip1
|
UTSW |
4 |
124,966,613 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1735:Snip1
|
UTSW |
4 |
124,964,994 (GRCm39) |
missense |
probably benign |
0.00 |
|
R7218:Snip1
|
UTSW |
4 |
124,966,712 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R7226:Snip1
|
UTSW |
4 |
124,965,273 (GRCm39) |
missense |
probably benign |
0.27 |
|
R7977:Snip1
|
UTSW |
4 |
124,960,732 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R7987:Snip1
|
UTSW |
4 |
124,960,732 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R7999:Snip1
|
UTSW |
4 |
124,965,174 (GRCm39) |
missense |
probably benign |
0.00 |
|
R8392:Snip1
|
UTSW |
4 |
124,960,618 (GRCm39) |
missense |
probably damaging |
0.99 |
|
| Protein Function and Prediction |
Overexpression of Snip1 inhibits the transcriptional activation of Smad4 and NF-κB by blocking their interactions with CBP/p300 (1;2). Snip1 is involved in the cotranscriptional or posttranscriptional regulation of cyclin D1 mRNA stability (3). Snip1 also associates with c-Myc, a regulator of cell proliferation and transformation; Snip1 enhances the transcriptional activity of c-Myc by both stabilizing it against degradation and by bridging it to p300 (4). The Snip1 protein contains an N-terminal nuclear localization signal and a C-terminal forkhead-associated domain (1). The N-terminus of Snip1 has been shown to interact with both the TGF-β family signaling protein Smad4 and the NF-κB transcription factor p65/RelA as well as the transcriptional coactivators CBP and p300 (1;2).
|
| Expression/Localization |
Northern blot analysis detected the ubiquitous expression of three transcripts (4.4, 2.4, and 1.5 kb); highest expression was in the heart and skeletal muscle (1). Western blot detected protein expression of Snip1 in all mouse tissues examined (1). Immunohistochemistry determined that Snip1 localized to epithelial elements in rat kidney sections; in a mouse mammary cell line, Snip1 localized to the nucleus (1).
|
| Background |
A mutation in SNIP1 (an A to G transition at 1097; E366G) is linked to psychomotor retardation, epilepsy, and craniofacial dysmorphism [OMIM: 614501; (5)].
|
| References |
1. Kim, R. H., Wang, D., Tsang, M., Martin, J., Huff, C., de Caestecker, M. P., Parks, W. T., Meng, X., Lechleider, R. J., Wang, T., and Roberts, A. B. (2000) A Novel Smad Nuclear Interacting Protein, SNIP1, Suppresses p300-Dependent TGF-Beta Signal Transduction. Genes Dev. 14, 1605-1616.
2. Kim, R. H., Flanders, K. C., Birkey Reffey, S., Anderson, L. A., Duckett, C. S., Perkins, N. D., and Roberts, A. B. (2001) SNIP1 Inhibits NF-Kappa B Signaling by Competing for its Binding to the C/H1 Domain of CBP/p300 Transcriptional Co-Activators. J Biol Chem. 276, 46297-46304.
3. Bracken, C. P., Wall, S. J., Barre, B., Panov, K. I., Ajuh, P. M., and Perkins, N. D. (2008) Regulation of Cyclin D1 RNA Stability by SNIP1. Cancer Res. 68, 7621-7628.
4. Fujii, M., Lyakh, L. A., Bracken, C. P., Fukuoka, J., Hayakawa, M., Tsukiyama, T., Soll, S. J., Harris, M., Rocha, S., Roche, K. C., Tominaga, S., Jen, J., Perkins, N. D., Lechleider, R. J., and Roberts, A. B. (2006) SNIP1 is a Candidate Modifier of the Transcriptional Activity of c-Myc on E Box-Dependent Target Genes. Mol Cell. 24, 771-783.
5. Puffenberger, E. G., Jinks, R. N., Sougnez, C., Cibulskis, K., Willert, R. A., Achilly, N. P., Cassidy, R. P., Fiorentini, C. J., Heiken, K. F., Lawrence, J. J., Mahoney, M. H., Miller, C. J., Nair, D. T., Politi, K. A., Worcester, K. N., Setton, R. A., Dipiazza, R., Sherman, E. A., Eastman, J. T., Francklyn, C., Robey-Bond, S., Rider, N. L., Gabriel, S., Morton, D. H., and Strauss, K. A. (2012) Genetic Mapping and Exome Sequencing Identify Variants Associated with Five Novel Diseases. PLoS One. 7, e28936. |
| Posted On |
2013-01-20 |
| Science Writer |
Anne Murray |
Incidental Mutation